CA2759874C - Methods of treating a pulmonary bacterial infection using fluoroquinolones - Google Patents
Methods of treating a pulmonary bacterial infection using fluoroquinolones Download PDFInfo
- Publication number
- CA2759874C CA2759874C CA2759874A CA2759874A CA2759874C CA 2759874 C CA2759874 C CA 2759874C CA 2759874 A CA2759874 A CA 2759874A CA 2759874 A CA2759874 A CA 2759874A CA 2759874 C CA2759874 C CA 2759874C
- Authority
- CA
- Canada
- Prior art keywords
- bacteria
- bacterial infection
- fluoroquinolone
- anaerobic conditions
- under anaerobic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000002685 pulmonary effect Effects 0.000 title claims abstract description 43
- 208000035143 Bacterial infection Diseases 0.000 title claims abstract description 37
- 208000022362 bacterial infectious disease Diseases 0.000 title claims abstract description 37
- 229940124307 fluoroquinolone Drugs 0.000 title claims description 18
- 238000000034 method Methods 0.000 title abstract description 23
- 241000894006 Bacteria Species 0.000 claims abstract description 48
- 239000003306 quinoline derived antiinfective agent Substances 0.000 claims abstract description 29
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims abstract description 23
- 229960003376 levofloxacin Drugs 0.000 claims abstract description 23
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229960001699 ofloxacin Drugs 0.000 claims abstract description 10
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 20
- 229910002651 NO3 Inorganic materials 0.000 claims description 15
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 15
- 241000589517 Pseudomonas aeruginosa Species 0.000 claims description 10
- 206010036790 Productive cough Diseases 0.000 claims description 8
- 208000024794 sputum Diseases 0.000 claims description 8
- 210000003802 sputum Anatomy 0.000 claims description 8
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 claims description 7
- 239000000443 aerosol Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 208000015181 infectious disease Diseases 0.000 description 22
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 11
- 229960003644 aztreonam Drugs 0.000 description 11
- WZPBZJONDBGPKJ-VEHQQRBSSA-N aztreonam Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C(O)=O)\C1=CSC([NH3+])=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-N 0.000 description 11
- 238000011282 treatment Methods 0.000 description 11
- 239000003242 anti bacterial agent Substances 0.000 description 10
- 230000000813 microbial effect Effects 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 229960000707 tobramycin Drugs 0.000 description 10
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 10
- 229960004821 amikacin Drugs 0.000 description 9
- LKCWBDHBTVXHDL-RMDFUYIESA-N amikacin Chemical compound O([C@@H]1[C@@H](N)C[C@H]([C@@H]([C@H]1O)O[C@@H]1[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O1)O)NC(=O)[C@@H](O)CCN)[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O LKCWBDHBTVXHDL-RMDFUYIESA-N 0.000 description 9
- 229940088710 antibiotic agent Drugs 0.000 description 9
- 238000009826 distribution Methods 0.000 description 8
- 239000004599 antimicrobial Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 6
- 206010021143 Hypoxia Diseases 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000001146 hypoxic effect Effects 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000001580 bacterial effect Effects 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 101150070420 gyrA gene Proteins 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000000845 anti-microbial effect Effects 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 108010052444 Oxyrase Proteins 0.000 description 2
- 239000008272 agar Substances 0.000 description 2
- 230000004099 anaerobic respiration Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000001717 pathogenic effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 238000010610 time kill assay Methods 0.000 description 2
- ZEUUPKVZFKBXPW-TWDWGCDDSA-N (2s,3r,4s,5s,6r)-4-amino-2-[(1s,2s,3r,4s,6r)-4,6-diamino-3-[(2r,3r,5s,6r)-3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-6-(hydroxymethyl)oxane-3,5-diol;sulfuric acid Chemical compound OS(O)(=O)=O.N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N ZEUUPKVZFKBXPW-TWDWGCDDSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 238000009635 antibiotic susceptibility testing Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000002815 broth microdilution Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- CAOOISJXWZMLBN-PPHPATTJSA-N htn0d03vrz Chemical compound Cl.C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 CAOOISJXWZMLBN-PPHPATTJSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229960004477 tobramycin sulfate Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Otolaryngology (AREA)
- Oncology (AREA)
- Dispersion Chemistry (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17262509P | 2009-04-24 | 2009-04-24 | |
| US61/172,625 | 2009-04-24 | ||
| PCT/US2010/032128 WO2010124141A1 (en) | 2009-04-24 | 2010-04-22 | Methods of treating a pulmonary bacterial infection using fluoro-quinolones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2759874A1 CA2759874A1 (en) | 2010-10-28 |
| CA2759874C true CA2759874C (en) | 2016-11-08 |
Family
ID=43011488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2759874A Active CA2759874C (en) | 2009-04-24 | 2010-04-22 | Methods of treating a pulmonary bacterial infection using fluoroquinolones |
Country Status (27)
| Country | Link |
|---|---|
| US (2) | US20120035166A1 (pt) |
| EP (1) | EP2421539B1 (pt) |
| JP (2) | JP6179844B2 (pt) |
| KR (1) | KR20120034626A (pt) |
| CN (2) | CN107050032A (pt) |
| AU (1) | AU2010238765B2 (pt) |
| BR (1) | BRPI1006626B8 (pt) |
| CA (1) | CA2759874C (pt) |
| CL (1) | CL2011002649A1 (pt) |
| CO (1) | CO6450642A2 (pt) |
| CY (1) | CY1122525T1 (pt) |
| DK (1) | DK2421539T3 (pt) |
| ES (1) | ES2755754T3 (pt) |
| HR (1) | HRP20191951T1 (pt) |
| HU (1) | HUE046595T2 (pt) |
| IL (1) | IL215777A (pt) |
| LT (1) | LT2421539T (pt) |
| MX (1) | MX339077B (pt) |
| MY (1) | MY178871A (pt) |
| NZ (1) | NZ596245A (pt) |
| PL (1) | PL2421539T3 (pt) |
| PT (1) | PT2421539T (pt) |
| RU (1) | RU2535056C2 (pt) |
| SG (3) | SG175288A1 (pt) |
| SI (1) | SI2421539T1 (pt) |
| WO (1) | WO2010124141A1 (pt) |
| ZA (1) | ZA201107903B (pt) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8524735B2 (en) * | 2005-05-18 | 2013-09-03 | Mpex Pharmaceuticals, Inc. | Aerosolized fluoroquinolones and uses thereof |
| HUE038428T2 (hu) | 2008-10-07 | 2018-10-29 | Horizon Orphan Llc | Aeroszol fluorokinolon készítmények javított farmakokinetika érdekében |
| WO2010042549A1 (en) | 2008-10-07 | 2010-04-15 | Mpex Pharmaceuticals, Inc. | Inhalation of levofloxacin for reducing lung inflammation |
| PT2473170T (pt) | 2009-09-04 | 2019-08-23 | Horizon Orphan Llc | Utilização de levofloxacina em aerossol para tratamento de fibrose cística |
| US9572774B2 (en) | 2011-05-19 | 2017-02-21 | Savara Inc. | Dry powder vancomycin compositions and associated methods |
| JP6426696B2 (ja) * | 2013-03-14 | 2018-11-21 | センプラ ファーマシューティカルズ，インコーポレイテッド | 呼吸器疾患の治療のための方法および製剤 |
| JP6966835B2 (ja) * | 2016-02-05 | 2021-11-17 | ホライズン オーファン リミテッド ライアビリティ カンパニー | 嚢胞性線維症のためのフルオロキノロン製剤 |
| CN108849939B (zh) * | 2018-07-31 | 2021-02-19 | 广东省农业科学院植物保护研究所 | 盐酸左氧氟沙星在制备用于防治烟草青枯病的农药制剂中的应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003075889A1 (en) | 2002-03-05 | 2003-09-18 | Transave, Inc. | An inhalation system for prevention and treatment of intracellular infections |
| RU2255757C1 (ru) * | 2004-06-22 | 2005-07-10 | Санкт-Петербургская Общественная Организация "Санкт-Петербургский Институт Биорегуляции И Геронтологии Сзо Рамн" | Пептидное соединение, восстанавливающее функцию органов дыхания |
| KR101488403B1 (ko) * | 2005-05-18 | 2015-02-04 | 엠펙스 파마슈티컬즈, 인코포레이티드 | 에어로졸화된 플루오로퀴놀론 및 이의 용도 |
| US7838532B2 (en) | 2005-05-18 | 2010-11-23 | Mpex Pharmaceuticals, Inc. | Aerosolized fluoroquinolones and uses thereof |
| AU2009246217B2 (en) * | 2008-05-15 | 2013-01-10 | Novartis Ag | Pulmonary delivery of a fluoroquinolone |
| HUE038428T2 (hu) * | 2008-10-07 | 2018-10-29 | Horizon Orphan Llc | Aeroszol fluorokinolon készítmények javított farmakokinetika érdekében |
-
2010
- 2010-04-22 WO PCT/US2010/032128 patent/WO2010124141A1/en active Application Filing
- 2010-04-22 SG SG2011076932A patent/SG175288A1/en unknown
- 2010-04-22 RU RU2011145430/15A patent/RU2535056C2/ru active
- 2010-04-22 SG SG10201811494SA patent/SG10201811494SA/en unknown
- 2010-04-22 CA CA2759874A patent/CA2759874C/en active Active
- 2010-04-22 MY MYPI2011005063A patent/MY178871A/en unknown
- 2010-04-22 LT LT10767800T patent/LT2421539T/lt unknown
- 2010-04-22 MX MX2011011190A patent/MX339077B/es active IP Right Grant
- 2010-04-22 BR BRPI1006626A patent/BRPI1006626B8/pt active IP Right Grant
- 2010-04-22 PT PT107678005T patent/PT2421539T/pt unknown
- 2010-04-22 DK DK10767800T patent/DK2421539T3/da active
- 2010-04-22 KR KR1020117027809A patent/KR20120034626A/ko active Search and Examination
- 2010-04-22 EP EP10767800.5A patent/EP2421539B1/en active Active
- 2010-04-22 HU HUE10767800A patent/HUE046595T2/hu unknown
- 2010-04-22 JP JP2012507400A patent/JP6179844B2/ja active Active
- 2010-04-22 NZ NZ596245A patent/NZ596245A/xx unknown
- 2010-04-22 SG SG10201403512TA patent/SG10201403512TA/en unknown
- 2010-04-22 CN CN201610900988.6A patent/CN107050032A/zh active Pending
- 2010-04-22 SI SI201031951T patent/SI2421539T1/sl unknown
- 2010-04-22 AU AU2010238765A patent/AU2010238765B2/en active Active
- 2010-04-22 CN CN2010800180220A patent/CN102427815A/zh active Pending
- 2010-04-22 ES ES10767800T patent/ES2755754T3/es active Active
- 2010-04-22 PL PL10767800T patent/PL2421539T3/pl unknown
-
2011
- 2011-10-21 US US13/278,706 patent/US20120035166A1/en not_active Abandoned
- 2011-10-23 IL IL215777A patent/IL215777A/en active IP Right Grant
- 2011-10-24 CL CL2011002649A patent/CL2011002649A1/es unknown
- 2011-10-29 ZA ZA2011/07903A patent/ZA201107903B/en unknown
- 2011-11-02 CO CO11148624A patent/CO6450642A2/es not_active Application Discontinuation
-
2015
- 2015-10-09 JP JP2015201285A patent/JP6228580B2/ja not_active Expired - Fee Related
-
2019
- 2019-10-28 HR HRP20191951TT patent/HRP20191951T1/hr unknown
- 2019-11-06 CY CY20191101155T patent/CY1122525T1/el unknown
-
2020
- 2020-02-20 US US16/796,525 patent/US20210015811A1/en not_active Abandoned
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